Hormone produced by moderate exercise could delay onset of
Alzheimer's

5 February 2013

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A stress hormone produced during moderate exercise may protect
the brain from memory changes related to Alzheimer’s disease. The
discovery, by a team at Nottingham University, may also explain why
people who are susceptible to stress are at more risk of developing the
disease.

Alzheimer’s disease is the most common cause of dementia affecting
almost 500,000 people in the UK, the majority of who are over the
age of 65. Symptoms can include memory loss, mood changes and
problems with communicating and reasoning.

There is no cure for Alzheimer’s and, although there are a few
treatments available that can reduce the symptoms in some people,
they cannot halt the progression of the disease.

Increasingly, there is evidence that physical and mental activity
can reduce people’s chances of developing the disease or can slow
down it’s progression but up until now it has been unclear how this
happens.

Protective effect

The Nottingham team, led by Dr Marie-Christine Pardon in the School
of Biomedical Sciences, has discovered that the stress hormone CRF —
or corticotrophin-releasing factor — may have a protective effect on
the brain from the memory changes brought on by Alzheimer’s disease.

CRF is most associated with producing stress and is found in high
levels in people experiencing some forms of anxiety and depressive
diseases. Normal levels of CRF, however, are beneficial to the
brain, keeping the mental faculties sharp and aiding the survival of
nerve cells. Unsurprisingly then, studies have shown that people
with Alzheimer’s disease have a reduced level of CRF.

The researchers used an experimental drug to prevent the hormone
from binding to a brain receptor called CRFR1 in mice with
Alzheimer’s disease that were free from memory impairments,
therefore blocking the effects of the hormone.

They discovered that the mice had an abnormal stress response with
reduced anxiety but increased behavioural inhibition when confronted
by a stressful situation — in this case being placed in a new
environment — and this is was due to the abnormal functioning of the
CRFR1. This abnormal stress response before the onset of symptoms
may explain why people susceptible to stress are more at risk of
developing Alzheimer’s.

Memory enhancing

Dr Pardon and her team also found that interrupting the hormone from
binding on to the CRFR1 receptor blocked the improvement of memory
normally promoted by exercise. However, in mice with Alzheimer’s a
repeated regime of moderate exercise restored the normal function of
the CRF system allowing its memory enhancing effects. The results
are in line with the idea that regular exercise is a means of
improving one’s ability to deal with everyday stress in addition to
keeping mental abilities keen.

Finally, their study showed that the switching on of this particular
brain receptor during exercise increased the density of synapses,
which makes the connection between nerve cells, the loss of which is
thought to be responsible for the early memory loss seen in
Alzheimer’s patients.

Dr Pardon said: “This is the first time that researchers have been
able to identify a brain process directly responsible for the
beneficial effects of exercise in slowing down the progression of
the early memory decline characteristics of Alzheimer’s disease.

“Overall, this research provides further evidence that a healthy
lifestyle involving exercise slows down the risk of Alzheimer’s
disease and opens avenues for the new interventions targeting the
altered CRFR1 function associated with the early stages of the
disease.”